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ClinicalTrials.gov Identifier: NCT02364336

Recruitment Status :
Completed

First Posted : February 18, 2015

Last Update Posted : August 9, 2018

Sponsor:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Information provided by (Responsible Party):

National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

- Chronic hepatitis B is caused by a virus that infects the liver. Cure is not possible but the virus can be controlled with the use of antiviral medicines,. Researchers think that adding a second antiviral medicine might help.

Objective:

- To understand how peginterferon might help treat people with chronic hepatitis B. Also, to see if peginterferon is safe to use with other antiviral medications.

Eligibility:

- Adults age 18 and older who have chronic hepatitis B and had therapy with 1 or more oral medicines for hepatitis B for at least 4 years.

Design:

Participants will be screened with physical exam and medical history. They will complete health questionnaires about their levels of fatigue and pain. They will have blood and urine tests. They may have an eye exam.

Participants also will have a Fibroscan. A test to measure how stiff your liver is.

Eligible participants will have a liver biopsy. Blood will be drawn.

Participants will be admitted to the NIH Clinical Center. They will be injected with the study drug. Then they will have a second liver biopsy. They will be discharged 24 hours later.

Participants will have 5 clinic visits during the 24-week treatment period. Then they will have follow-up visits every 12 weeks for 48 weeks.

During visits, participants may have a physical exam and medical history. They may have blood and urine tests. They may have a Fibroscan and complete questionnaires. At the final visit, they will also have a Fibroscan.

Condition or disease

Intervention/treatment

Phase

Chronic Hepatitis B

Drug: Peginterferon alfa-2a

Phase 2

Detailed Description:

Chronic hepatitis B virus (HBV) infection is a leading cause of liver associated morbidity and mortality. Currently available first-line therapies for treatment of chronic hepatitis B include pegylated interferon-alpha and the nucleos(t)ide analogues (NUCs) entecavir and tenofovir. These were shown to effectively suppress viral replication, but their ability to induce durable off-treatment response is limited to a small subset of patients. Combination treatment with peginterferon and NUCs has been attempted in several randomized controlled trials, with no apparent advantage over either agent given alone. In these studies however, treatment with peginterferon was initiated either simultaneously or shortly after NUCs administration. The efficacy of peginterferon following long-term viral suppression with NUCs was only tested in one small pilot study, nevertheless showing 60% HBsAg loss rate.

The underlying mechanisms responsible for improved efficacy of peginterferon in this setting are unknown and warrant further investigation. In this single arm study we propose to evaluate the efficacy and mechanisms associated with response to peginterferon add-on therapy following a minimum of 192 weeks of viral suppression induced by NUCs in a group of chronic HBV infected patients. Sixty patients with either HBeAg positive (n=30) or negative (n=30) chronic HBV infection will be enrolled to this study. After medical evaluation and pretreatment liver biopsy, treatment with subcutaneous injections of pegylated interferon alpha-2a 180 g per week will be given for a total of 24 weeks, followed by an off-treatment evaluation period of 48 weeks. A second liver biopsy will be performed six hours following the first peginterferon injection. Primary end-point for this study will be the change in interferon-stimulated-genes response before and after first interferon injection in responders versus non-responders to treatment. The responsiveness to IFN-based therapy of treatment responders vs nonresponders will additionally be evaluated by studying intrahepatic and peripheral blood natural killer cells. The study will also assess HBeAg and HBsAg loss and seroconversion rates in comparison to historical controls treated with either peginterferon or NUCs monotherapy. Finally, we will assess whether treatment responders develop an HBV-specific T cell response similar in quantity and quality to that of patients who spontaneously resolve HBV infection.

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Ages Eligible for Study:

18 Years to 80 Years (Adult, Older Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

INCLUSION CRITERIA:

Inclusion criteria: HBeAg positive group

Age >18 years and older, male or female.

Known serum HBsAg and HBeAg positivity at the time of screening.

Ongoing treatment with one or more NUCs for at least 192 weeks before study entry. Subjects may have a brief interruption of treatment for medical reasons (e.g. breast feeding) not to exceed 8 weeks and none within the 48 weeks before study entry.

ALT level less than or equal to 2 ULN based on at least two determinations taken at least one month apart during the 24 weeks before study entry with the second being at time of screening

Written informed consent

Inclusion criteria: HBeAg negative group

Age >18 years and older, male or female.

Known serum HBsAg positivity and HBeAg negativity at the time of screening.

Ongoing treatment with one or more NUCs for at least 192 weeks before study entry. Subjects may have a brief interruption of treatment for medical reasons (e.g. breast feeding) not to exceed 8 weeks and none within the 48 weeks before study entry.

ALT level less than or equal to 2 ULN based on at least two determinations taken at least one month apart during the 24 weeks before study entry with the second being at time of screening

Written informed consent

EXCLUSION CRITERIA:

Exclusion criteria (for both eAg positive and negative patients)

Co-infection with HDV as defined by the presence of anti-HDV in serum and/or HDV antigen in the liver.

Co-infection with HCV as defined by the presence of HCV RNA in serum.

Co-infection with HIV as defined by the presence of anti-HIV in serum.

Decompensated liver disease as defined by serum bilirubin >2.5 mg/dL (with direct bilirubin > 0.5 mg/dL), prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3 g/dL, or a history of ascites, variceal bleeding or hepatic encephalopathy.

A history of organ transplantation or in the absence of organ transplantation, any immunosuppressive therapy requiring the use of more than 5 mg of prednisone (or its equivalent) daily.

Significant systemic illness other than liver diseases including congestive heart failure, renal failure, chronic pancreatitis and diabetes mellitus with poor control, that in the opinion of the investigator may interfere with therapy.

Pregnancy or inability to practice contraception in patients capable of bearing or fathering children

Lactating women.

Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the liver that is suggestive of HCC, or an alpha-fetoprotein level of greater than 500 ng/mL.